Research Progress on Pharmacological Effects of Lycorine Hydrochloride

Lycoris radiata,a Chinese herbal medicine,is a plant of Amaryllidaceae family,which has the antidotal,expectorant,diuretic,emetic and insecticidal effects.Lycorine hydrochloride is an alkaloid extracted from the bulb of L.radiata.Studies have shown that lycorine hydrochloride has many pharmacological effects(anti-fungal,anti-viral and anti-tumor).In this paper,the related research on pharmacological effects and mechanism of lycorine hydrochloride is systematically summarized in order to provide a theoretical basis for further research and application of lycorine hydrochloride.

LC-MS/MS Analysis of Lycorine and Galantamine in Human Serum Using Pentafluorophenyl Column

Lycorine and galantamine are natural alkaloids found in Amaryllidaceae plants, such as narcissus. Narcissus leaves and roots are sometimes accidentally ingested because they resemble vegetables. Lycorine and galantamine are toxic and cause such effects as nausea, vomiting, and abdominal pain, when accidentally ingested. In a case of narcissus poisoning, the detection of lycorine and galantamine in biological samples is vital to determine whether they have been ingested. This study establishes a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to measure the lycorine and galantamine content of human serum, which can be used for mild to fatal poisoning cases. A serum pretreatment procedure was performed using acetonitrile and QuEChERS AOAC powder. The separation of the compounds was conducted using a pentafluorophenyl column, CAPCELL CORE PFP (2.1 mm I.D. × 100 mm, 2.7 μm). Lycorine, galantamine, and galantamine-d6 (internal standard) were identified by the transitions of m/z 288 → 147, m/z 288 → 213, and m/z 294 → 216, respectively. The calibration curves were linear in the ranges of 0.05 to 5 ng/mL and 5 to 100 ng/mL, with R2 > 0.999. The precision and accuracy were within the permissible range. The matrix effects of lycorine and galantamine were 94.3% - 98.4% and 87.8% - 91.1%, respectively. The extraction recovery rates of lycorine and galantamine were 101.9% - 112.7% and 95.6% - 107.1%, respectively. The present method detected lycorine and galantamine in the sera of three patients with mild poisoning that had accidentally ingested. This method is applicable in cases of lycorine and galantamine poisoning.

Lycorine derivative effectively inhibits the replication of coronaviruses both in vitro and in vivo

The established and ongoing prevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and seasonal human coronaviruses(HCoV)like HCoV-OC43,HCoV-NL63,and HCoV-229E,pose a continuous threat to public health.Therefore,it is urgently needed to explore antiviral drugs with broad-spectrum anti-coronavirus activity.Our previous studies have revealed that lycorine is a potent broad-spectrum anti-coronavirus drug,a natural alkaloid extracted from Amaryllidaceae with various pharmacological and microbiological effects.However,it is unsafe to directly use lycorine as a clinical antiviral drug due to the cytotoxicity and induction of cell apoptosis.In this study,a series of lycorine derivatives were designed and synthesized.One of them,named Ly-8,was found to effectively inhibit the replication of different coronavirus strains in vitro,including SARS-CoV-2.Moreover,Ly-8 was also shown to effectively inhibit HCoVOC43 replication in the central nervous system,and provide effective protection against HCoV-OC43 infection in mice with low drug toxicity.Furthermore,Ly-8-resistant mutants were not observed during the 30 times sequential passages in cell culture.Collectively,these findings suggest that Ly-8 may be a potential candidate drug for the future development of broad-spectrum anti-coronavirus drugs.

Lycorine inhibits breast cancer growth and metastasis via inducing apoptosis and blocking Src/FAK-involved pathway

Breast cancer is the most commonly diagnosed cancer type worldwide among women and more than 90% of patients die from tumor metastasis. Lycorine, a natural alkaloid, has been widely reported possessing potential efficacy against cancer proliferation and metastasis. In our study, the anti-tumor potency on breast cancer was evaluated in vitro and in vivo for the first time. Our results indicated that lycorine inhibited breast cancer cells growth, migration and invasion as well as induced their apoptosis.In in vivo study, lycorine not only suppressed breast tumor growth in xenograft models and inhibited breast tumor metastasis in MDA-MB-231 tail vein model. More importantly, we found lycorine had less toxicity than first-line chemotherapy drug paclitaxel at the same effective dose in vivo. Furthermore, on mechanism, lycorine inhibited tumor cell migration and invasion via blocking the Src/FAK(focal adhesion kinase)-involved pathway. In conclusion, our study implied lycorine was a potential candidate for the treatment of breast cancer by inhibition of tumor growth and metastasis.

In Vitro Inhibition of Alphaviruses by Lycorine

Chikungunya virus(CHIKV) is a mosquito-borne alphavirus. As an emerging virus, CHIKV imposes a threat to public health. Currently, there are no vaccines or antivirals available for the prevention of CHIKV infection. Lycorine, an alkaloid from Amaryllidaceae plants, has antiviral activity against a number of viruses such as coronavirus, flavivirus and enterovirus. In this study, we found that lycorine could inhibit CHIKV in cell culture at a concentration of 10 lmol/L without apparent cytotoxicity. In addition, it exhibited broad-spectrum anti-alphavirus activity, including Sindbis virus(SINV),Semliki Forest virus(SFV), and Venezuelan equine encephalomyelitis virus(VEEV). The time of addition studies indicated that lycorine functions at an early post-entry stage of CHIKV life cycle. The results based on two different CHIKV replicons provided further evidence that lycorine exerts its antiviral activity mainly by inhibiting CHIKV translation.Overall, our study extends the antiviral spectrum of lycorine.

(±)-Lycorane关键中间体的合成研究

以DL-羟基脯氨酸为起始原料,经EDCl偶联、LiBH4还原、Dess-Martin氧化,Wit-tig反应和环氧化反应等步骤,合成得到构筑Lycorine型生物碱ABD环碳骨架的关键中间体7,总收率为40.1%.化合物7的结构经1H NMR和MS表征得到确认,为进一步开展Lycorine型生物碱的全合成新路线研究奠定了物质基础.